crossing96/oncoscreening huggingface dataset:
Potential plasma biomarkers of bladder cancer identified by proteomic analysis: A pilot study.	BACKGROUND: Bladder cancer diagnosis and surveillance includes cystoscopy and cytology. New methods for the detection of bladder cancer are needed, because cystoscopy is invasive and expensive, and because urine cytology is not sensitive enough. OBJECTIVES: The aim of the study was to select potential plasma protein markers for bladder cancer which could be useful in developing a specific laboratory test to improve diagnosis and to establish treatment strategies in order to prevent the recurrence of the disease. MATERIAL AND METHODS: Plasma proteome maps were prepared based on 2-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), combined with image gel analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of plasma samples from patients with urothelial bladder cancer, and they were compared to normal samples. RESULTS: The analyses of bladder cancer plasma samples allowed us to distinguish 3 groups of proteins whose relative abundance differed from that in normal samples. The 1st one comprised modified forms of plasma transferrin, fibrinogen gamma and complement C3b, which were absent in normal plasma. The 2nd group comprised haptoglobin, alpha-2-macroglobulin, vitamin D-binding protein, and pigment epithelium-derived factor, which occurred in the cancerous samples in large quantities. The 3rd group consisted of 3 molecular forms of immunoglobulin M (IgM), the relative abundance of which was significantly lower in the cancerous plasma samples. CONCLUSIONS: The data indicated potential plasma biomarkers associated with inflammation, immunity and coagulation processes accompanying bladder cancer. They could be used for the development of a laboratory test(s) useful in clinical practice.	bladder
Identification of an enhancer region within the TP63/LEPREL1 locus containing genetic variants associated with bladder cancer risk.	PURPOSE: Genome-wide association studies (GWAS) have led to the identification of a bladder cancer susceptibility variant (rs710521) in a non-coding intergenic region between the TP63 and LEPREL1 genes on chromosome 3q28, suggesting a role in the transcriptional regulation of these genes. In this study, we aimed to functionally characterize the 3q28 bladder cancer risk locus. METHODS: Fine-mapping was performed by focusing on the region surrounding rs710521, and variants were prioritized for further experiments using ENCODE regulatory data. The enhancer activity of the identified region was evaluated using dual-luciferase assays. CRISPR/Cas9-mediated deletion of the enhancer region was performed and the effect of this deletion on cell proliferation and gene expression levels was evaluated using CellTiter-Glo and RT-qPCR, respectively. RESULTS: Fine-mapping of the GWAS signal region led to the identification of twenty SNPs that showed a stronger association with bladder cancer risk than rs710521. Using publicly available data on regulatory elements and sequences, an enhancer region containing the bladder cancer risk variants was identified. Through reporter assays, we found that the presence of the enhancer region significantly increased ΔNTP63 promoter activity in bladder cancer-derived cell lines. CRISPR/Cas9-mediated deletion of the enhancer region reduced the viability of bladder cancer cells by decreasing the expression of ΔNTP63 and p63 target genes. CONCLUSIONS: Taken together, our data show that bladder cancer risk-associated variants on chromosome 3q28 are located in an active enhancer region. Further characterization of the allele-specific activity of the identified enhancer and its target genes may lead to the identification of novel signaling pathways involved in bladder carcinogenesis.	bladder
STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non-Muscle-Invasive Bladder Cancer.	"Purpose: Most bladder cancers are early-stage tumors known as papillary non-muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified STAG2 as among the most commonly mutated genes in NMIBC and provided initial evidence in a pilot cohort that STAG2-mutant tumors recurred less frequently than STAG2 wild-type tumors. Here, we report a STAG2 biomarker validation study using two independent cohorts of clinically annotated papillary NMIBC tumors from the United States and Europe.Experimental Design: The value of STAG2 immunostaining for prediction of recurrence was initially evaluated in a cohort of 82 patients with papillary NMIBC (""Georgetown cohort""). Next, the value of STAG2 immunostaining for prediction of progression to muscle invasion was evaluated in a progressor-enriched cohort of 253 patients with papillary NMIBC (""Aarhus cohort"").Results: In the Georgetown cohort, 52% of NMIBC tumors with intact STAG2 expression recurred, whereas 25% of STAG2-deficient tumors recurred (P = 0.02). Multivariable analysis identified intact STAG2 expression as an independent predictor of recurrence (HR = 2.4; P = 0.05). In the progressor-enriched Aarhus cohort, 38% of tumors with intact STAG2 expression progressed within 5 years, versus 16% of STAG2-deficient tumors (P < 0.01). Multivariable analysis identified intact STAG2 expression as an independent predictor of progression (HR = 1.86; P = 0.05).Conclusions: STAG2 IHC is a simple, binary, new assay for risk stratification in papillary NMIBC. Clin Cancer Res; 24(17); 4145-53. ©2018 AACR."	bladder
Breast cancer metastasis to the bladder: a literature review.	Given the prevalence of breast cancer and the mortality associated with metastatic disease, it is imperative for physicians to not only be aware of common sites but also of rare metastatic destinations such as the bladder. A postmenopausal woman with a medical history of stage 2 invasive ductal carcinoma, oestrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative, in remission for 9 years, presented to her primary care physician with concerns of increased urinary urgency, frequency and incontinence. The patient underwent cystoscopy with biopsy of an area of granulation tissue. Biopsy revealed adenocarcinoma consistent with breast primary. The common sites of metastases from breast cancer are lung, bone and liver. This case is unique where breast cancer was found to metastasise to the bladder. It is important for physicians to consider further investigation when a breast cancer survivor develops urinary symptoms even without haematuria.	bladder
Quantitative Proteomic Analysis Identifies AHNAK (Neuroblast Differentiation-associated Protein AHNAK) as a Novel Candidate Biomarker for Bladder Urothelial Carcinoma Diagnosis by Liquid-based Cytology.	Cytological examination of urine is the most widely used noninvasive pathologic screen for bladder urothelial carcinoma (BLCA); however, inadequate diagnostic accuracy remains a major challenge. We performed mass spectrometry-based proteomic analysis of urine samples of ten patients with BLCA and ten paired patients with benign urothelial lesion (BUL) to identify ancillary proteomic markers for use in liquid-based cytology (LBC). A total of 4,839 proteins were identified and 112 proteins were confirmed as expressed at significantly different levels between the two groups. We also performed an independent proteomic profiling of tumor tissue samples where we identified 7,916 proteins of which 758 were differentially expressed. Cross-platform comparisons of these data with comparative mRNA expression profiles from The Cancer Genome Atlas identified four putative candidate proteins, AHNAK, EPPK1, MYH14 and OLFM4. To determine their immunocytochemical expression levels in LBC, we examined protein expression data from The Human Protein Atlas and in-house FFPE samples. We further investigated the expression of the four candidate proteins in urine cytology samples from two independent validation cohorts. These analyses revealed AHNAK as a unique intracellular protein differing in immunohistochemical expression and subcellular localization between tumor and non-tumor cells. In conclusion, this study identified a new biomarker, AHNAK, applicable to discrimination between BLCA and BUL by LBC. To our knowledge, the present study provides the first identification of a clinical biomarker for LBC based on in-depth proteomics.	bladder
Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era.	"INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the ""pre-immunotherapy era"") and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC. RESULTS: There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P < 0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013. CONCLUSION: Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease."	bladder
Modeling human bladder cancer.	INTRODUCTION: Bladder cancer is a major public health concern and the treatment options available are unable to significantly prevent disease recurrence and progression. The need for experimental tumor models to efficiently reproduce the pathology of human cancers has prompted researchers to attempt various approaches. METHODS: A PubMed search combining the MeSH bladder cancer and models was executed in March 2017. RESULTS: We review the advantages and limitations of currently available in vitro 2D and 3D bladder cancer models as well as in vivo rodent models. To date, despite the description of a variety of animal models (including transplantable, carcinogen-induced and genetically engineered models), the establishment of reliable, simple, practicable and reproducible animal models remains an ongoing challenge. Recently, sophisticated 3D culture systems have been designed to better recapitulate the phenotypic and cellular heterogeneity as well as microenvironmental aspects of in vivo tumor growth, while being more flexible to conduct repeated experiments. CONCLUSION: Selecting the most appropriate model for a specific application will maximize the conversion of potential therapies from the laboratory to clinical practice and requires an understanding of the various models available.	bladder
Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers with Response to Neoadjuvant Chemotherapy.	The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy benefits overall survival for patients with muscle-invasive bladder cancer (MIBC). However, the relationship between the genetic profiling of MIBC and NAC response remains unclear. Here, a mutation panel of six cancer-associated genes (TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC) panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin α3β1 (AG) and CK5/6) were developed. BC samples from patients who showed a pathologic response (n = 39) and non-response (n = 13) were applied to the panel analysis. ERBB2, FGFR3 and PIK3CA exclusively altered in the responders group (19/39, 48.7%), in which FGFR3 mutations were significantly enriched in patients with a response in the cohort (14/39, 35.9%; P = 0.01). Additionally, strong expression of ERCC1 was associated with a pathologic response (P = 0.01). However, positive lymph node metastasis (P < 0.01) and lymph-vascular invasion (LVI) (P = 0.03) were correlated with a non-response. Overall, the data show that FGFR3 mutations and elevated expression of ERCC1 in MIBCs are potential predictive biomarkers of the response to NAC.	bladder
Hexvix plus Chemo.	While photodynamic diagnosis during transurethral resection of bladder tumor seems warranted only in seemingly high-risk cases, early intravesical instillation of chemotherapy is warranted in all low-risk cases. According to the latest randomized controlled trial, data may make sense also in intermediate- and high-risk cases.	bladder
Treatment and outcomes of urethral recurrence after orthotopic neobladder replacement in patients with bladder cancer - practice in a single centre.	Objectives To report on the treatment of urethral recurrence after orthotopic urinary diversion at our institution. Methods We retrospectively reviewed clinical information of urethral recurrence in patients who underwent radical cystectomy and orthotopic urinary diversion between January 1998 and January 2013. Results Of 341 patients, 282 presented for follow-up (median follow-up: 56 months; range: 1-174 months). Eight patients developed local recurrence of urothelial cancer after radical cystectomy. The rate of urethral recurrence (1.4%) in female patients who underwent orthotopic urinary diversion was lower than in male patients (3.3%). The median (range) time to recurrence was 33 (6-120) months after radical cystectomy and orthotopic urinary diversion. Recurrences were treated by transurethral resection of tumour, urethrectomy, neobladder resection, revision of urinary diversion, adjuvant chemotherapy, or radiation therapy, based on individual circumstances. Survival analysis showed that 5-year cancer-specific survival was significantly higher in patients with urethral recurrence alone (83.3%), compared with patients with other recurrences, including pelvic/abdomen recurrence and distant metastasis (26.8%). Conclusions En bloc urethrectomy and revision of urinary diversion remain the principle surgical choices. Selection of transurethral tumour resection was based on tumour stage and was used in carefully chosen patients. Cancer-specific survival might depend on multidisciplinary therapy.	bladder
Under-stage and Overlook of Peritoneal Spread from Bladder Urothelial Carcinoma.	BACKGROUND/AIM: Bladder cancer can spread from the sub-peritoneal space superior and posterolateral to the peritoneal cavity via the peritoneal lining. The aim of this study was to improve the identification of peritoneal spread from bladder urothelial carcinoma based on computed tomography (CT) scans. MATERIALS AND METHODS: This is a retrospective study including patients selected with the following criteria: (i) pathology-confirmed urothelial carcinoma; (ii) peritoneal spread identified on CT scans from axial and corona views, either initially or after radical/partial cystectomy, concomitant chemoradiotherapy (CCRT), or radiotherapy. One hundred and fifty-nine cases met the selection criteria. RESULTS: Routes of spread to the peritoneum included the superior to anterior direction in 59 patients (37%), the superior to posterolateral direction in 19 (12%), and the superior to both anterior and posterolateral directions in 81 (51%). Invasion of specific sites included the abdominal wall in 101 patients (70%), bowel/mesentery in 84 (53%), prostate, uterus, and rectum in 30 (19%), and circumferential tumors that outlined the whole bladder wall in 59 (37%). Initial modes of therapy were chemotherapy in 86 patients (54%), cystectomy in 55 (35%), CCRT in eight (5%), radiotherapy in two (1%), and no therapy in eight (5%). Peritoneal spread due to under-staging (clinical/pathological stage) after local therapy was found in 84 patients (53%). CONCLUSION: Initial pre-therapeutic staging is easily overlooked regarding peritoneal spread from bladder urothelial carcinoma. Combined axial and coronal views of CT scans can help identify peritoneal involvement.	bladder
The use of blue light flexible cystoscopy with hexaminolevulinate & the diagnosis of bladder cancer.	Blue light cystoscopy improves the detection of bladder cancer at time of transurethral resection of bladder tumor for nonmuscle-invasive bladder cancer. This has translated to decreased tumor recurrence. Given this improvement in rigid cystoscopy, the question remains whether the use of blue light flexible cystoscopy (BLFC) in the surveillance setting provides the same benefits. This review aims to evaluate the recently reported Phase III prospective multicenter study of BLFC which evaluated the detection of bladder cancer during surveillance, which in its earliest reporting demonstrated improved detection of bladder cancer. This study evaluated 304 patients with findings of 63 confirmed malignancies, with 13 (20.6%) only identified by BLFC (p < 0.0001). The question still remains whether the improved detection rate will translate to improved clinical outcomes. Further, studies will be necessary to determine which patients will benefit from BLFC, optimal ways to incorporate into surveillance strategies and cost-effectiveness.	bladder
miR-96 regulates migration and invasion of bladder cancer through epithelial-mesenchymal transition in response to transforming growth factor-β1.	Bladder cancer (BC) is one of the most frequent urological malignancies, and its molecular mechanism still remains unclear. Recent studies have revealed that MicroRNA (miRNAs) acted as oncogenes or tumor suppressors in a variety of cancers. MiRNA-96 has been reported to play a significant role in the development and progression of many cancers. In the current study, we found that transforming growth factor (TGF)-β1 played a significant role in the progression that miR-96 conducted. And TGF-β1 could also regulate the expression of FOXQ1, which is the target gene of miR-96. Furthermore, miR-96 induced epithelial-mesenchymal transition in BC cells, which is driven by TGF-β1. In conclusion, our data revealed that miR-96 regulates the progression and epithelial-mesenchymal transition, which is driven by TGF-β1 in BC cells; it may provide a new thought for the therapy of BC.	bladder
Biomarkers of aggressiveness in genitourinary tumors with emphasis on kidney, bladder, and prostate cancer.	Over the last decade, the improvement in molecular techniques and the acquisition of genomic information has transformed and increased the quality of patient care and our knowledge of diseases. Areas covered: Protein expression levels in immunohistochemistry and molecular biomarkers are reported for their ability to predict recurrence, progression, development of metastases, or patient survival. In particular, for renal cell carcinoma, we take into consideration the biomarkers applicable to immunohistochemistry and with molecular and genetic analyses. In urothelial carcinoma, there is great interest in the possibility of distinguishing the basal vs. luminal subtypes and to acquire deeper insight into the tumor biology through examining exosomes in urine and biomarkers in the serum. In prostate cancer, single gene expression and multiple gene expression classifiers are reviewed as a tool to distinguish indolent vs. aggressive disease. Expert commentary: The genomic information along with the application of ancillary techniques allow the definition of a neoplasia not only by its morphology but also by its biological signature. This continuous increase in knowledge will result in a better comprehension of oncogenesis, development of targeted therapies and optimizing decision-making processes related to patient care.	bladder
Bladder cancer recurrence surveillance by urine metabolomics analysis.	Non Muscle Invasive Bladder Cancer (NMIBC) is among the most frequent malignant cancers worldwide. NMIBC is treated by transurethral resection of the bladder tumor (TURBT) and intravesical therapies, and has the highest recurrence rate among solid tumors. It requires a lifelong patient monitoring based on repeated cystoscopy and urinary cytology, both having drawbacks that include lack of sensitivity and specificity, invasiveness and care costs. We conducted an investigative clinical study to examine changes in the urinary metabolome of NMBIC patients before and after TURBT, as well during the subsequent surveillance period. Adjusting by prior probability of recurrence per risk, discriminant analysis of UPLC-MS metabolic profiles, displayed negative predictive values for low, low-intermediate, high-intermediate and high risk patient groups of 96.5%, 94.0%, 92.9% and 76.1% respectively. Detailed analysis of the metabolome revealed several candidate metabolites and perturbed phenylalanine, arginine, proline and tryptophan metabolisms as putative biomarkers. A pilot retrospective analysis of longitudinal trajectories of a BC metabolic biomarkers during post TURBT surveillance was carried out and the results give strong support for the clinical use of metabolomic profiling in assessing NMIBC recurrence.	bladder
Intravesical BCG treatment causes a long-lasting reduction of recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer.	PURPOSE: To analyse if BCG treatment leads to long-term reduction of recurrence, progression, and cancer-specific mortality (CSM) in patients with high-risk NMIBC. MATERIALS AND METHODS: 140 patients with high-risk NMIBC were drawn from a population-based cohort of 538 patients with newly diagnosed bladder cancer in the Stockholm County between 1995 and 1996. Data were collected prospectively, and a final follow-up for recurrence, progression, and CSM was performed after 15 years. Patients that received BCG were compared with patients who did not receive BCG. Survival analysis was done with Kaplan-Meier estimates and Mantel-Cox log-rank test. Multivariable Cox proportional regression with stepwise selection was performed to verify the statistical significance of clinicopathological factors of prognostic importance. Results were displayed in Hazard ratios and a p < 0.05 was considered to be statistically significant. RESULTS: With a median follow-up of 100 months (2-182), 76 patients recurred; 50 progressed to muscle invasion; and 92 died of whom 38 died from bladder cancer. After 15-year follow-up, there was a statistically significant reduction in rate for recurrence (HR 0.40, p < 0.0001) and progression (HR 0.52, p = 0.038), but not for CSM, in patients that received BCG compared to those who did not. CONCLUSIONS: In this group, BCG in high-risk NMIBC patients reduced the long-term risk of recurrence and progression. The effect on CSM is yet to be clarified.	bladder